A cohort of anti-human immunodeficiency virus (HIV) positive donors and controls has been under prospective follow-up since 1985 (N Engl J Med 321:917, 1989). At enrollment, 182 subjects were Western blot (WB) positive, including 159 asymptomatic donors, 15 blood recipients, and 9 sexual partners. A control population included 70 anti-HIV reactive donors who were WB negative and 21 who were WB indeterminate. Of the 159 WB positive donors, 46 (25%) are alive and in active follow-up; 72(45%)are dead, and 41(26%)are lost to follow-up(LTFU);13 of the 73 LTFU were known to have AIDS at the time they left the study. Of the 46 in active followup, 25 (54%) have had an AIDS defining event. Of the 72 dead, 61 (85%)died from an AIDS-related illness, 92% of which occurred before HAART therapy became available. In contrast, only 5 of 59 (8%) surviving sufficiently long to receive HAART succumbed to HIV infection. There is a significant difference between the mean CD4 count at entry for those alive (510 cells/ml) and those dead (391 cells/ml) and the entry HIV RNA level (3.17 log copies/ml and 3.77 log copies/ml, respectively). There are three treatment-naive long-term (>10 years)non-progressors (LTNP), none of whom were homozygous for the CCR5-delta-32 mutation. No factors have been identified that distinguish the LTNP from the rest of the cohort. . indicated. In contrast to published studies, no survival advantage of coexistent GBV-C/HGV infection has been observed in this cohort. No evidence of HIV infection evolved in the initial anti-HIV positive, but WB-indeterminate or WB-negative subjects. Treatment with HAART therapy is being conducted by personal physicians or through other NIH protocols. In summary, this cohort of HIV infected blood donors died largely of AIDS before the advent of HAART. The impact of HAART on those who lived to receive therapy has been dramatic.